Objective To investigate the role and molecular mechanism of SOX4 in Helicobacter pylori(H.pylori)-mediated gastric mucosal epithelial dysplasia.Methods The expression of SOX4 in gastric tissues and cells was analyzed with reverse transcription-polymerase chain reaction(RT-PCR),Western blotting,and immunohistochemical staining.The effects of SOX4 on gastric epithelial cell proliferation and colony formation were determined with CCK-8 and colony formation assays.A PCR array was used to screen downstream target genes involved in H.pylori-induced dysplasia mediated by SOX4.The transcriptional regulation and binding sites of the target gene MLH3 by SOX4 were elucidated with luciferase reporter assay,promoter truncation assay,and chromatin immunoprecipitation(ChIP).Results SOX4 expression was significantly increased in H.pylori-infected gastric tissues(P<0.05).Overexpression of SOX4 markedly enhanced the proliferation and colony formation abilities of normal gastric epithelial cells(P<0.05).Elevated SOX4 led to the dysregulation of MLH3 and other DNA damage repair-related molecules after H.pylori infection in gastric epithelial cells(|logFC|>1,P<0.05).H.pylori promoted MLH3 expression in gastric epithelial cells through SOX4.SOX4 transcriptionally activated MLH3 expression by binding to the 5th site of the MLH3 promoter.The increased expression of SOX4 and MLH3 is associated with poor prognosis of gastric cancer patients.Conclusion SOX4 is closely associated with H.pylori-induced dysplasia in gastric epithelial cells.Upregulation of SOX4 promotes H.pylori-related dysplasia by transcriptionally activating MLH3,leading to the imbalance of proliferation and colony formation in gastric epithelial cells.

Objective To investigate the role and molecular mechanism of SOX4 in Helicobacter pylori(H.pylori)-mediated gastric mucosal epithelial dysplasia.Methods The expression of SOX4 in gastric tissues and cells was analyzed with reverse transcription-polymerase chain reaction(RT-PCR),Western blotting,and immunohistochemical staining.The effects of SOX4 on gastric epithelial cell proliferation and colony formation were determined with CCK-8 and colony formation assays.A PCR array was used to screen downstream target genes involved in H.pylori-induced dysplasia mediated by SOX4.The transcriptional regulation and binding sites of the target gene MLH3 by SOX4 were elucidated with luciferase reporter assay,promoter truncation assay,and chromatin immunoprecipitation(ChIP).Results SOX4 expression was significantly increased in H.pylori-infected gastric tissues(P<0.05).Overexpression of SOX4 markedly enhanced the proliferation and colony formation abilities of normal gastric epithelial cells(P<0.05).Elevated SOX4 led to the dysregulation of MLH3 and other DNA damage repair-related molecules after H.pylori infection in gastric epithelial cells(|logFC|>1,P<0.05).H.pylori promoted MLH3 expression in gastric epithelial cells through SOX4.SOX4 transcriptionally activated MLH3 expression by binding to the 5th site of the MLH3 promoter.The increased expression of SOX4 and MLH3 is associated with poor prognosis of gastric cancer patients.Conclusion SOX4 is closely associated with H.pylori-induced dysplasia in gastric epithelial cells.Upregulation of SOX4 promotes H.pylori-related dysplasia by transcriptionally activating MLH3,leading to the imbalance of proliferation and colony formation in gastric epithelial cells.

Objective:To identify risk factors associated with endoscopic atrophic progression of gastric mucosa after Helicobacter pylori ( HP) eradication and to develop a risk scoring system for establishing an individualized endoscopic follow-up strategy for patients with chronic gastritis. Methods:This retrospective cohort study included chronic gastritis patients with successful HP eradication at the Department of Gastroenterology, Beijing Friendship Hospital between January 2018 and October 2021. Demographic characteristics, endoscopic findings, and other clinical data were analyzed. Endoscopic outcomes of gastric mucosal atrophy before and after follow-up were compared to classify patients into progression and non-progression groups. Univariate and multivariate analyses were performed to identify independent risk factors for endoscopic atrophic progression. A risk scoring system was then constructed based on these factors. Results:A total of 218 patients with chronic gastritis were included, including 153 in the non-progression group and 65 in the progression group. Multivariate logistic regression analysis showed that gastric ulcer ( P=0.008, OR=4.24, 95% CI: 1.46-12.25), history of proton pump inhibitor use ( P=0.007, OR=4.06, 95% CI: 1.46-11.27), alcohol consumption ( P=0.002, OR=3.77, 95% CI: 1.64-8.67), high-salt diet ( P=0.008, OR=2.90, 95% CI: 1.32-6.41), and high red meat intake ( P=0.025, OR=2.33, 95% CI: 1.11-6.31) were independent risk factors for endoscopic atrophic progression after HP eradication. The predictive model based on these 5 factors demonstrated strong discriminative capacity, with an area under the receiver operating characteristic curve of 0.813 (95% CI: 0.755-0.876, P<0.001). The optimal cut-off value was 1.5 points, stratifying patients into low-risk (0-2 points) and high-risk (3-5 points) groups. Conclusion:Patients with chronic gastritis remain susceptible to progression even after successful HP eradication. Individualized endoscopic follow-up strategies should be considered based on patients' medical history, medication use, lifestyle, and dietary habits.

Objective:To identify risk factors associated with endoscopic atrophic progression of gastric mucosa after Helicobacter pylori ( HP) eradication and to develop a risk scoring system for establishing an individualized endoscopic follow-up strategy for patients with chronic gastritis. Methods:This retrospective cohort study included chronic gastritis patients with successful HP eradication at the Department of Gastroenterology, Beijing Friendship Hospital between January 2018 and October 2021. Demographic characteristics, endoscopic findings, and other clinical data were analyzed. Endoscopic outcomes of gastric mucosal atrophy before and after follow-up were compared to classify patients into progression and non-progression groups. Univariate and multivariate analyses were performed to identify independent risk factors for endoscopic atrophic progression. A risk scoring system was then constructed based on these factors. Results:A total of 218 patients with chronic gastritis were included, including 153 in the non-progression group and 65 in the progression group. Multivariate logistic regression analysis showed that gastric ulcer ( P=0.008, OR=4.24, 95% CI: 1.46-12.25), history of proton pump inhibitor use ( P=0.007, OR=4.06, 95% CI: 1.46-11.27), alcohol consumption ( P=0.002, OR=3.77, 95% CI: 1.64-8.67), high-salt diet ( P=0.008, OR=2.90, 95% CI: 1.32-6.41), and high red meat intake ( P=0.025, OR=2.33, 95% CI: 1.11-6.31) were independent risk factors for endoscopic atrophic progression after HP eradication. The predictive model based on these 5 factors demonstrated strong discriminative capacity, with an area under the receiver operating characteristic curve of 0.813 (95% CI: 0.755-0.876, P<0.001). The optimal cut-off value was 1.5 points, stratifying patients into low-risk (0-2 points) and high-risk (3-5 points) groups. Conclusion:Patients with chronic gastritis remain susceptible to progression even after successful HP eradication. Individualized endoscopic follow-up strategies should be considered based on patients' medical history, medication use, lifestyle, and dietary habits.

Background::Non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) have shown similar worsening epidemic patterns globally and shared various overlapping pathophysiological mechanisms. However, evidence on the relationship between NAFLD and IBD risk is lacking. We aimed to investigate the associations between long-term risk of incident IBD and NAFLD in a large prospective cohort.Methods::Participants from the United Kingdom Biobank cohort (https://biobank.ndph.ox.ac.uk/) who were free of IBD and alcoholic liver disease at baseline were enrolled. Baseline non-alcoholic fatty liver degree was measured by the well-established fatty liver index (FLI). The outcomes of interest included incident IBD, ulcerative colitis (UC), and Crohn’s disease (CD). Multivariable Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).Results::Among 418,721 participants (mean FLI: 48.11 ± 30.11), 160,807 (38.40%) participants were diagnosed as NAFLD at baseline. During a median of 12.4 years’ follow-up, 2346 incident IBD cases (1545 UC, 653 CD, and 148 IBD-unclassified) were identified. Due to limited events, those IBD-unclassified were combined in UC or CD when examining the associated risk of UC or CD, separately. Compared with the lowest quartile of FLI, the highest quartile showed a separately 36.00%, 25.00%, and 58.00% higher risk of incident IBD (HR Q4 vs. Q1 =1.36, 95% CI: 1.19-1.55, Ptrend <0.001), UC (HR Q4 vs. Q1 =1.25, 95% CI: 1.07-1.46, Ptrend=0.047), and CD (HR Q4 vs. Q1 =1.58, 95% CI: 1.26-1.97, Ptrend <0.001) after multivariable adjustment. Compared with non-NAFLD, NAFLD participants had a significantly higher risk of incident IBD (HR=1.13, 95% CI: 1.04-1.24) and CD (HR =1.36, 95% CI: 1.17-1.58). Conclusions::Higher degree of non-alcoholic fatty liver is associated with increased risk of incident IBD. Interventions aimed at improving NAFLD may be a potential targeted strategy for the detection and treatment of IBD.

Objective:To assess the correlation and consistency between the cancer risk-oriented endoscopic Kimura-Takemoto classification and the operative link for gastritis assessment (OLGA) in risk stratification of gastric cancer in patients with chronic gastritis after Helicobacter pylori ( H. pylori) eradication. Methods:From January 1, 2018 to October 31, 2021, 97 patients with chronic gastritis who successfully underwent H. pylori eradication at Beijing Friendship Hospital affiliated to Capital Medical University were selected. During the follow-up period, all patients underwent standardized magnifying endoscopy to assess gastric mucosal atrophy with the Kimura-Takemoto classification, which was classified as no or mild atrophy, moderate atrophy, and severe atrophy. Additionally, according to the new Sydney staging system, endoscopic biopsies were conducted at 5 sites of the patients to classify into OLGA stages 0, Ⅰ, Ⅱ, Ⅲ, or Ⅳ. Spearman rank correlation analysis and Kappa consistency test were performed to evaluate the correlation and consistency between the 2 evaluation systems, respectively. Area under the curve (AUC) of the receiver operating characteristic curve was used to calculate the predictive ability of the grading of gastric mucosal atrophy under endoscopy in high-risk histological staging. Furthermore, multivariate logistic regression analysis was used to assess factors influencing the consistency of the 2 evaluation systems. Chi-square test or Fisher′s exact test were used for statistical analysis. Results:Longitudinal follow-up was completed in 97 cases, with a follow-up time of (37.38±13.18) months after H. pylori eradication. The proportion of OLGA stage Ⅲ to Ⅳ in patients with no or mild atrophy (21.7%, 10/46) was lower than that in patients with moderate and severe atrophy (63.0%, 29/46 and 5/5, respectively), and the differences were statistically significant( χ2=16.07 and 13.30, both P<0.001). However, there was no significant difference in distribution of OLGA staging between patients with moderate atrophy and patients with severe atrophy (all P>0.05). The consistency rate of high-risk assessment for gastric cancer between the 2 evaluation systems was 73.2% (71/97). The correlation between the Kimura-Takemoto classification and OLGA staging was moderate ( r=0.47, 95% confidence interval(95% CI) 0.30 to 0.61, P<0.001). The result of consistency test indicated that the consistency of the 2 evaluation systems was moderate, and the Kappa value was 0.46 (95% CI 0.29 to 0.64, P<0.001). For patients with chronic gastritis after H. pylori eradication, the sensitivity of Kimura-Takemoto classification of moderate to severe atrophy under endoscopy in identifying high-risk of OLGA stages was 77.21% (95% CI 62.16% to 88.53%), the specificity was 69.81% (95% CI 55.66% to 81.66%), and the AUC was 0.735 (95% CI 0.636 to 0.820, P<0.01). As the time after H. pylori eradication increased (post- H. pylori eradication less than 18, 18 to 36, and more than 36 months), the consistency of atrophy assessment between the Kimura-Takemoto classification and OLGA staging reduced (7/8, 84.4% (27/32), 64.9% (37/57), respectively), and the difference was statistically significant ( χ2=4.36, P=0.037). The result of multivariate logistic regression analysis revealed that the time after H. pylori eradication more than 36 months ( OR=3.443, 95% CI 1.117 to 10.614, P=0.031) and gastric ulcer ( OR=3.928, 95% CI 1.177 to 13.110, P=0.026) were independent factors influencing the consistency between the Kimura-Takemoto classification and OLGA staging. Conclusions:The endoscopic and histological changes of chronic gastritis after eradication of H. pylori are consistent. Within short period after H. pylori eradication (no more than 36 months), the sensitivity of high-risk classification under endoscopy is high and the specificity is moderate, which can predict high-risk histological staging to a certain degree.

Objective:To evaluate the effects of hemoclips on preventing delayed bleeding for early gastric cancer (EGC) after endoscopic submucosal dissection (ESD).Methods:Clinical data of 459 patients who underwent ESD for EGC in Beijing Friendship Hospital from June 2013 to August 2020 were collected retrospectively. Patients were divided into group A (hemoclip group, n=162) and group B (non-hemoclip group, n=297) according to whether preventive hemostatic clip treatment was performed after resection. Delayed bleeding within 2 weeks after ESD was observed. Univariate analysis and subgroup analysis were conducted for the delayed bleeding incidence and clinicopathological features. Results:Delayed bleeding incidences of group A and group B were 3.1% (5/162) and 8.1% (24/297) with significant difference between the two groups ( χ2=4.418, P=0.036). Subgroup analysis showed that there were significant differences in the delayed bleeding incidence between the two groups when the diameter of the tumor >20 mm [3.5% (2/57) VS 15.3% (13/85), χ2=5.016, P=0.025], the tumor located in the lower part of the stomach [1.0% (1/97) VS 10.4% (20/192), χ2=8.425, P=0.004], and the depth of tumor invasion was M/SM1 [3.2% (5/157) VS 8.1% (23/285), χ2=4.072, P=0.044]. There were no significant differences in the delayed bleeding incidence between group A and group B when the diameter of the tumor ≤20 mm, the tumor located in the upper/medial part of the stomach and the depth of tumor invasion was SM2 ( P>0.05). Conclusion:Hemoclips can prevent delayed bleeding after ESD for EGC, which is mainly observed in a tumor of diameter >20 mm, located in the lower part of the stomach and M/SM1 tumor invasion. It has little effect on the prevention when the tumor diameter ≤20 mm and located in the upper/medial part of the stomach.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is the endoscopic modality of choice for the treatment of biliary and pancreatic diseases. However, patients with cirrhosis, particularly those with decompensated cirrhosis, are believed to be at increased risk for complications associated with ERCP. There is a paucity of literature describing the outcomes of ERCP for patients with cirrhosis. This study aimed to investigate the outcomes of ERCP for cirrhosis patients, especially adverse events, and evaluated its safety and efficacy. METHODS: We performed a multicenter, retrospective study of all patients at Beijing Friendship Hospital affiliated to Capital Medical University, Xijing Hospital affiliated to Air Force Military Medical University, Beijing Youan Hospital affiliated to Capital Medical University, and the Fifth Medical Center of the People's Liberation Army General Hospital from June 2003 to August 2019. The adverse events of inpatient ERCP for patients with ( n  = 182) and without liver cirrhosis (controls; n  = 385) were compared. RESULTS: A total of 567 patients underwent ERCP between January 2003 and December 2019 were enrolled in this study. Compared to patients without cirrhosis, patients with cirrhosis were at higher risk for postoperative complications (odds ratio [OR], 4.172; 95% confidence interval [CI], 1.232-7.031; P  < 0.001) such as postoperative pancreatitis (OR, 2.026; 95% CI, 1.002-4.378; P  = 0.001) and cholangitis (OR, 3.903; 95% CI, 1.001-10.038; P  = 0.036). The main indications for ERCP for patients with cirrhosis in this study included choledocholithiasis (101 cases; 55.5%), benign bile duct strictures (46 cases; 25.3%), and malignant bile duct strictures (28 cases; 15.4%). Among them, 23 patients (12.6%) underwent balloon dilation and 79 patients (43.4%) underwent sphincterotomy. Of the patients with cirrhosis, delayed bleeding occurred in ten patients (5.5%), postoperative pancreatitis occurred in 80 patients (44.0%), and postoperative cholangitis occurred in 25 patients (13.7%). An additional multivariate analysis showed that the total bilirubin (TBIL) level (OR, 4.58; 95% CI, 2.37-6.70) and Child-Pugh score of C (OR, 3.11; 95% CI, 1.04-5.37) were risk factors for postoperative complications in patients with cirrhosis. CONCLUSIONS Compared with the general population of patients undergoing ERCP, patients with cirrhosis were more prone to postoperative pancreatitis and cholangitis. TBIL levels and Child-Pugh scores were risk factors for postoperative complications in patients with cirrhosis.
Humans ; Cholangiopancreatography, Endoscopic Retrograde/adverse effects* ; Retrospective Studies ; Constriction, Pathologic ; Risk Factors ; Liver Cirrhosis/complications* ; Pancreatitis/etiology* ; Postoperative Complications/epidemiology* ; Cholangitis

Objective:To evaluate the efficacy and safety of SPOT (GI Supply, USA), a new carbon-based permanent marker approved by the Food and Drug Administration (FDA), in the endoscopic marking for gastrointestinal lesions.Methods:A total of 115 patients with gastrointestinal lesions who underwent endoscopic treatment or surgery in Beijing Friendship Hospital or Beijing Chao-Yang Hospital from April 2019 to November 2019 were enrolled in the study. SPOT was used to mark the lesions, and marking points were found during endoscopic treatment or surgery to calculate the effective marking rate by single-group target value method. Adverse events after marking were recorded, and the changes of blood routine test, liver and kidney functions before and after marking were compared.Results:The effective rate of endoscopic marking with SPOT was 99.13% (114/115). The longest marking time was 57 days. There was no puncture of intestinal wall or injection into abdominal cavity during the marking process. One patient developed mild fever after marking. The incidence of adverse events was 23.48% (27/115), which were all unrelated to the test equipment. There was no significant difference in blood routine tests or liver and kidney functions before and after marking ( P>0.05). Conclusion:SPOT produced by GI Supply can effectively mark gastrointestinal lesions without serious adverse events, which meets the requirements of clinical use.

Objective:To compare the efficacy of oral sulfate solution (OSS) and polyethylene glycol (PEG) electrolyte powder for colonoscopy bowel preparation.Methods:A total of 283 randomized patients from 9 centers in China taking OSS ( n=143) or PEG ( n=140) using two-day split bowel preparation regimen received colonoscopy and assessment. The primary index was the bowel preparation success rate [global Boston bowel preparation scale (BBPS)≥ 6 by independent assessment center]. Secondary indices included BBPS global and segmental scores, investigator satisfaction (5-point Likert scale) with the quality of bowel preparation, patient satisfaction assessed by questionnaires, and patient tolerance assessed by Sharma scale. Compliance and safety were compared between the two groups. Results:The bowel preparation success rates were 100.0% for OSS and 99.3% for PEG [adjusted difference 0.7% (95% CI: -5.3% - 6.7%), P<0.001 for non-inferiority]. The BBPS global score in OSS group was significantly higher than that in PEG group (8.1 VS 7.7, P<0.001). The segment BBPS scores were also higher in OSS group than those in PEG group for all 3 segments (right colon: 2.4 VS 2.3, P=0.002; transverse colon: 2.8 VS 2.7, P=0.018; left colon: 2.8 VS 2.7, P=0.007). Investigator Likert score in the OSS group was significantly higher than that in the PEG group (2.6 VS 2.3, P<0.001). There was no significant difference in compliance between OSS and PEG, except for the second dose (90.9% VS 82.6%, P=0.039). There was no significant difference in patient satisfaction, Sharma score or proportion of patients with tolerance-related symptoms between the two groups. Safety was comparable between the two groups, and all adverse events were mild to moderate. Conclusion:OSS has comparable efficacy with PEG, with higher BBPS scores in all segments, better investigator satisfaction, better compliance in split dose, and comparable patient tolerance and safety.